Submissions for variant NM_005148.4(UNC119):c.281G>A (p.Arg94Gln)

gnomAD frequency: 0.00003  dbSNP: rs763481567

Total submissions: 4

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Illumina Laboratory Services, Illumina	RCV001128387	SCV001287826	benign	Cone-rod dystrophy	2017-10-26	criteria provided, single submitter	clinical testing	This variant was observed as part of a predisposition screen in an ostensibly healthy population. A literature search was performed for the gene, cDNA change, and amino acid change (where applicable). No publications were found based on this search. Allele frequency data from public databases was too high to be consistent with this variant causing disease. Therefore, this variant is classified as benign.
Labcorp Genetics (formerly Invitae), Labcorp	RCV001309225	SCV001498719	uncertain significance	not provided	2024-10-25	criteria provided, single submitter	clinical testing	This sequence change replaces arginine, which is basic and polar, with glutamine, which is neutral and polar, at codon 94 of the UNC119 protein (p.Arg94Gln). This variant is present in population databases (rs763481567, gnomAD 0.07%), and has an allele count higher than expected for a pathogenic variant. This variant has not been reported in the literature in individuals affected with UNC119-related conditions. ClinVar contains an entry for this variant (Variation ID: 892399). An algorithm developed to predict the effect of missense changes on protein structure and function (PolyPhen-2) suggests that this variant is likely to be disruptive. In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance.
Ambry Genetics	RCV004032277	SCV003939157	uncertain significance	not specified	2023-05-31	criteria provided, single submitter	clinical testing	The c.281G>A (p.R94Q) alteration is located in exon 2 (coding exon 2) of the UNC119 gene. This alteration results from a G to A substitution at nucleotide position 281, causing the arginine (R) at amino acid position 94 to be replaced by a glutamine (Q). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear.
PreventionGenetics, part of Exact Sciences	RCV004746249	SCV005358378	likely benign	UNC119-related disorder	2024-04-17	no assertion criteria provided	clinical testing	This variant is classified as likely benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications).